The Office for Protection from Research Risks
(OPRR) fulfills responsibilities set forth in the U.S. Public
Health Service Act. These include (i) developing and monitoring
guidance relative to regulations of the U.S. Department of Health
and Human Services (DHHS) - one of several Executive Branch
Departments and Agencies bound by common minimum standards for
the protection of human research subjects; (ii) exercising
compliance oversight; and (iii) establishing criteria for and
negotiation of assurances to comply submitted by institutions
that are to engage in DHHS-conducted or supported research prior
to involvement of human subjects.

In brief, ethical standards, Institutional Review Board (IRB)
functions, and informed consent expectations are generally
compatible with those of the International Ethical Guidelines for
Biomedical Research Involving Human Subjects which were published
in 1993 by the Council for International Organizations of Medical
Sciences (CIOMS) in collaboration with the World Health
Organization (WHO).

In general, OPRR requires (i) prior assurances to abide by
minimal ethical, IRB, and consent standards as a prior condition
to begin; (ii) that changes in IRB membership reported as they
occur; (iii) reasonable provision for IRB reviews to be
knowledgeable about the immediate context in which subjects
participate; (iv) that subjects not be involved in research
without prior IRB approval; and (v) full board convened IRB
meetings for initial and continuing reviews of clinical trials.
All institutions engaged in DHHS-conducted or supported research
must be found by OPRR to comply with at least equivalent
protective procedures, regardless of national or international
location.

The jurisdiction of OPRR frequently overlaps with that of the
U.S. Food and Drug Administration (FDA), an agency with which
international investigators may be more familiar. Administrative
requirements for the protection of subjects were designed to be
comparable where common definitions, procedures, and minimum
expectations of both the FDA and OPRR are involved. However, the
different missions of the two agencies are accompanied by
differences in requirements, notably OPRR's requirement
for prior written assurance to comply with relevant regulations.
The degree of OPRR oversight prior to initiation of research
depends on the nature of the research and OPRR's
prior experience with the judgment of an institution's
IRB.

Several formats exist for an institution to assure compliance,
depending on the nature of the institution and/or the type of
research activity in which it is engaged; however, the basic
concept is the same. Assurance documents can be: (i) limited to
an individual DHHS-conducted or supported research protocol; (ii)
include certain groups of multi-site, multi-protocol studies; or
(iii) apply to all research of a specified class (e.g.,
biomedical or behavioral) which is undertaken at established
research centers. Much of DHHS's
international research is conducted or supported by the National
Institutes of Health (NIH) or the Centers for Disease Control and
Prevention (CDC). OPRR has conducted business in about 110
countries which are distributed across all six inhabited
continents.